The results obtained in this project indicate that prostaglandins (PGs) are likely to modulate the secretion of glucagon and insulin in some physiological (and therefore also some pathological) conditions. The proposed studies are designed to uncover the mechanisms of the modulation of pancreatic islet hormone secretion by endogenous PGs and to establish whether altering the availability of precursors of PGs by diet may influence islet hormone secretion in animals and man. Lipids and fatty acids will be measured by thin-layer and gas chromatography. Prostaglandins, glucagon and insulin will be measured by radioimmunoassay. In vitro experiments will be conducted, using the models of isolated perfused rat pancreas and the isolated rat islets. Prostaglandin biosynthesis will be augmented by providing arachidonic acid, or inhibited pharmacologically, and associated changes in basal and stimulated hormone secretion will be assessed. Conversely, hormone-secretory processes will be augmented or inhibited by various pharmalogical compounds, and associated changes in PG metabolism will be assessed. Prostaglandin metabolism and islet hormone secretion will be studied in vitro and in vivo in rats fed essential fatty-acid-deficient diets that will be supplemented with fish oil or corn oil to induce deficiency or abundance of PGs, respectively. The degree to which altering the availability of PG precursors affects hormone secretion and carbohydrate metabolism will be assessed in healthy subjects and patients with not-insulin-dependent diabetes mellitus who will be given dietary supplements of fish oil or corn oil. The thorough definition of the relationship between pancreatic PG metabolism and secretion of glucagon and insulin may enhance the understanding of some of the mechanisms of islet hormone secretion, provide clues for pathogenesis of some forms of diabetes, and suggest rational dietary management of diabetes.